LRRC15影响A549细胞自噬的作用研究

特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)是一种致病原因不明、进行性、慢性不可逆的间质性肺疾病。为探讨富含亮氨酸重复蛋白15(leucine-rich repeat-containing protein 15,LRRC15)在IPF的作用及调节机制,本研究构建了博来霉素(bleomycin,BLM)诱导的小鼠肺纤维化和A549细胞损伤模型,检测了LRRC15的表达变化。转染siLRRC15后分别采用MTT、GFP-RFP-LC3双荧光标记系统和免疫印迹等方法检测了细胞活性和自噬的变化。结果表明:BLM处理后,小鼠肺组织和A549细胞中LRRC15表达显著上调;将设计和合成的siLRRC15转入A549细胞,LRRC15的表达极显著降低,可以部分恢复BLM引起的细胞损伤;BLM处理A549细胞后,LC3-Ⅱ和P62蛋白呈现上升的趋势;GFP-RFP-LC3双荧光标记检测发现,BLM处理后自噬体数量明显增多;进一步用siLRRC15处理A549细胞后发现,自噬关键蛋白LC3-Ⅱ、ATG5、ATG7的表达增加,P62蛋白表达下调,自噬流的强度增加。以上研究结果说明LRRC15是IPF中上皮细胞损伤的指示剂,可能通过调节自噬参与纤维化过程中的调节,本研究为进一步阐明IPF的机制提供了必要的理论依据。

Studies of Sulphur- and Iron-induced Copper Deficiency in Tibetan Sheep

The clinical signs of Tibetan sheep with sulphur- and iron-induced copper deficiency in Maqu County of Gansu Province were defined as thin, decreased appetite, neonatal ataxia, pica, emaciation, and loss of hair color and anemia. The mineral composition of soil and forage, and samples of liver, blood and hair from Tibetan sheep in affected ranches in this region were compared with those from unaffected areas. The mean concentration of iron in soil and forage in affected pasture was 19 675 ±791 and 1 763 ±197 μg/g, respectively, compared with 8 761 ±871 and 357 ±39 μg/g in unaffected pasture. The mean concentration of sulphur in soil and forage in affected pasture was 1.98% ±0.79% and 0.88% ±0.16%, respectively, compared with 1.16%±0.26% and 0.47%±0.16%in unaffected pasture. The mean copper concentrations in soil and forage from the affected pastures were 15.9±1.8 and 6.7±1.6 μg/g, respectively, compared with 16.7±1.9 and 8.9±2.7 μg/g in unaffected pasture.The mean concentration of Cu in blood, liver, and hair from the affected Tibetan sheep were 0.32±0.12, 51.2±3.1 and 2.16±0.65μg/g, respectively, compared with 0.76±0.21, 191±11 and 3.27±0.96 μg/g for healthy animals. Oral administration of CuClO(OH)3prevented and cured anemia. We conclude that wool eating of Tibetan sheep in this region is probably caused by secondary Cu deficiency, mainly due to the high iron and sulphur contents in soils and forage.

Multivariate analysis of serum surface-enhanced Raman spectroscopy of liver cancer patients

Early diagnosis of liver cancer plays a significant role in reducing its high mortality.In this preliminary study,the feasibility of using serum surface-enhanced Raman spectroscopy(SERS)to identify liver cancer was studied.Serum samples were obtained from liver cancer patients and healthy controls.The differences between the SERS spectra of pre-operation and postoperation of liver cancer patients were also analyzed.The general shape and trend of SERS spectra of health control and liver cancer patients were similar.Multivariate analysis,e.g.,PLSSVM,might be useful for the discrimination of serum SERS spectra of pre-operation and post-operation.

Plasma non-transferrin-bound iron uptake by the small intestine leads to intestinal injury and intestinal flora dysbiosis in an iron overload mouse model and Caco-2 cells

Iron overload often occurs during blood transfusion and iron supplementation, resulting in the presence of non-transferrin-bound iron(NTBI) in host plasma and damage to multiple organs, but effects on the intestine have rarely been reported. In this study, an iron overload mouse model with plasma NTBI was established by intraperitoneal injection of iron dextran. We found that plasma NTBI damaged intestinal morphology, caused intestinal oxidative stress injury and reactive oxygen species(ROS) accumulation,and induced intestinal epithelial cell apoptosis. In addition, plasma NTBI increased the relative abundance of Ileibacterium and Desulfovibrio in the cecum, while the relative abundance of Faecalibaculum and Romboutsia was reduced. Ileibacterium may be a potential microbial biomarker of plasma NTBI. Based on the function prediction analysis, plasma NTBI led to the weakening of intestinal microbiota function, significantly reducing the function of the extracellular structure. Further investigation into the mechanism of injury showed that iron absorption in the small intestine significantly increased in the iron group. Caco-2 cell monolayers were used as a model of the intestinal epithelium to study the mechanism of iron transport. By adding ferric ammonium citrate(FAC, plasma NTBI in physiological form) to the basolateral side, the apparent permeability coefficient(Papp) values from the basolateral to the apical side were greater than 3×10^(-6)cm s^(-1). Intracellular ferritin level and apical iron concentration significantly increased, and SLC39A8(ZIP8) and SLC39A14(ZIP14) were highly expressed in the FAC group.Short hairpin RNA(sh RNA) was used to knock down ZIP8 and ZIP14 in Caco-2 cells. Transfection with ZIP14-specific sh RNA decreased intracellular ferritin level and inhibited iron uptake. These results revealed that plasma NTBI may cause intestinal injury and intestinal flora dysbiosis due to the uptake of plasma NTBI from the basolateral side into the small intestine, which is probably mediated by ZIP14.

PIC catalysis based on polyoxometalates promoting 5-HMF oxidation in H_(2)O/MIBK biphase

Novel polyoxometalate(POM)Pickering interfacial catalyst(PIC)was fabricated through loading(NH_(4))_(5)H_(6)PMo_(4)V_(8)O_(40)(PMo_(4)V_(8))on both alkyl and alkyl-amino groups functionalized silica nanoparticles.PMo_(4)V_(8)/SiO_(2)(C_(8)/C_(8)NH_(2)with molar ratio as 1:1)PIC system provided a new catalytic model for aerobic conversion of 5-hydroxymethylfurfural(5-HMF),as well as its recovery and product separation in H_(2)O/methyl isobutyl ketone(MIBK)biphase reaction.Balancing the ratio of PMo_(4)V_(8),C_(8)and C_(8)NH_(2)gave rise to variety in hydrophilicity and hydrophobicity for PMo_(4)V_(8)/SiO_(2)(C_(8)/C_(8)NH_(2)),which enhanced the transformation of 5-HMF to 2,5-diformylfuran(DFF)in H_(2)O/MIBK with 73.7%yield at 81.8%conversion than in H_(2)O or MIBK single phase.

Bifidobacterium adolescentis orchestrates CD143^(+)cancer-associated fibroblasts to suppress colorectal tumorigenesis by Wnt signaling-regulated GAS1

Background The interplay between gut microbiota and tumor microenvironment(TME)in the pathogenesis of colorectal cancer(CRC)is not well explored.Here,we elucidated the functional role of Bifidobacterium adolescentis(B.a)on CRC and investigated its possible mechanism on the manipulation of cancer-associated fibroblasts(CAFs)in CRC.Methods Different CRC animal models and various cell line models were established to explore the function of B.a on CRC.The single-cell RNA sequencing(scRNA-seq)or flow cytometry was used to detect the cell subsets in the TME of CRC.Western blot,quantitative real-time polymerase chain reaction(qRT-PCR),or immunofluorescence staining were performed to examine the activation of Wnt signaling and growth arrest specific 1(GAS1)on CD143+CAFs.Chromatin immunoprecipitation quantitative real-time PCR(CHIP-qPCR)was performed to investigate the regulation of transcription factor 4(TCF4)on GAS1.Multi-immunofluorescence assay examined the expression level of CD143 and GAS1 on tissue microarray.Results We found that B.a abundance was significantly reduced in CRC patients from two independent cohorts and the bacteria database of GMrepo.Supplementation with B.a suppressed ApcMin/+spontaneous or AOM/DSS-induced tumorigenesis in mice.scRNA-seq revealed that B.a facilitated a subset of CD143+CAFs by inhibiting the infiltration of Th2 cells,while promoting the TNF-alpha+B cells in TME.CD143+CAFs highly expressed GAS1 and exhibited tumor suppressive effect.Mechanistically,GAS1 was activated by the Wnt/β-catenin signaling in CD143+CAFs.B.a abundance was correlated with the expression level of CD143 and GAS1.The level of CD143+CAFs predicted the better survival outcome in CRC patients.Conclusions These results highlighted that B.a induced a new subset of CD143+CAFs by Wnt signaling-regulated GAS1 to suppress tumorigenesis and provided a novel therapeutic target for probiotic-based modulation of TME in CRC.

Event-triggered adaptive finite time trajectory tracking control for an under actuated vessel considering unknown time-varying disturbances

This paper aims to solve the finite-time trajectory tracking problem of underactuated surface ships under the influence of dynamic uncertainty,unknown external time-varying interference and limited communication resources.An event-triggered robust adaptive finite-time trajectory tracking control method for underactuated ships is designed by combining the existing trajectory tracking control methods and engineering needs in actual navigation.It can obviously improve the tracking accuracy of the ship,and complete the tracking task safely and efficiently.This scheme transforms the composite uncertain vector synthesized by uncertain parameters and external disturbances into a linear parameterized form.Next,considering the limitation of communication resources,a relative threshold event triggering mechanism is introduced to further extend the triggering time interval on the basis of the fixed threshold triggering scheme.Then,an event-triggered robust adaptive finite-time trajectory tracking control scheme is designed for underactuated ships,and a rigorous stability proof is provided through Lyapunov stability theory.Simulation experiment is carried out in MATLAB and the results show that the finite-time trajectory tracking control scheme proposed in this paper can effectively solve the problems of dynamic uncertainty.unknown time-varying external interference and limitation of communication resources.This paper can provide theoretical support for the autonomous navigation of intelligent ships.

Recent advances in photodynamic therapy based on emerging two-dimensional layered nanomaterials

Photodynamic therapy(PDT)is a promising non-invasive therapy approach for various diseases including malignant tumor.The process of PDT involves three interrelated aspects,namely photosensitizer(PS),light source,and oxygen,among which PS is the decisive factor that determines its anticancer efficiency.There exist some defects in currently applied PDT,such as inadequate production of reactive oxygen species(ROS),poor penetration of exciting light,insufficient oxygen supply,and nonselective distribution of PS.With unique physicochemical and optical properties,two-dimensional nanomaterials(2DNMs)have aroused great interest in biomedical fields.2DNMs-based PDT is promising to significantly improve antitumor efficacy compared to conventional PDT.In this review,we will firstly introduce the underlying mechanism of PDT and how 2DNMs are absorbed and distribute inside tumor cells.After that,we will not only illustrate how 2DNMs-based PDT can enhance tumor-killing efficacy and minimize side-effects through conquering the above-mentioned defects of conventional PDT and the preparation process of 2DNMs,but also elaborate recent advances about 2DNMs-based PDT.Lastly,we will summarize the challenges and future prospects of 2DNMs-based PDT.

Surface micro-texture on sapphire fabricated by laser ablation trajectory regulation

Fabrication of the surface micro-texture on the C-plane sapphire is undertaken by a355 nm Ultraviolet(UV)pulsed laser.The surface micro-textures of sapphire with different laser scanning line spacing ranging from 10 lm to 100 lm are obtained,where the selection range of scanning line spacing is controlled in the range of the groove width and plasma width to obtain a surface of high Peak-Valley(PV)value.A reasonable processing order is proposed to manufacture different types of surface micro-textures on sapphire by laser ablation trajectory regulation.In the multiple-passes laser ablation of sapphire by the UV nanosecond pulsed laser,the scanning lines in each direction is treated as once scanning.On this basis,the multiple processing can be carried out to avoid the influence of the subsequent scanning on the machined groove.In addition,the effect of different scanning line spacing on the PV value is quantified and different types of surface microtextures on sapphire,including the squares,the rhombuses and the hexagons,are successfully fabricated,which can be applied in the friction reduction or anti-reflection field.

血清表面增强拉曼光谱筛查肝癌的实验研究

文中探讨了使用血清表面增强拉曼光谱(SERS)区分健康志愿者与肝癌患者的可行性血清取自30名健康人,25名肝癌患者和25名治疗后肝癌患者,对其SERS光谱进行比较,并分析了生物医学意义。此外,主成分分析-线性判别分析(PCA-LDA),偏最小二乘判别分析(PLS-DA),K最近邻(KNN),人工神经网络(ANN)和支持向量机(SVM)算法具有高斯径向基函数(RBF)同时用于对血清进行分类。PCA-LDA,PLS-DA,PLS-KNN,PLS-SVM和PLS-ANN算法分别呈现出76%,90%,92%,94%和96%的准确性。初步研究结果表明血清SERS可用于肝癌筛查。